Immunoglobulin‐specific T‐B cell interaction. IV. B cell presentation of idiotypic determinant(s) of monoclonal anti‐surface immunoglobulin antibody to idiotope‐recognizing helper T clones

Abstract

Previously, we have demonstrated T-B cell interactions mediated by T cell recognition of immunoglobulin (Ig) peptide/major histocompatibility complex (MHC) class II complexes derived by the B cell processing of endogenously synthesized Ig molecules. In this report Ig-specific T-B cell interaction mediated by B cell presentation of idiotopes (Id) of anti-sIg antibodies to Id-specific T cell clones has been studied in Ig kappa-1-congenic rat strains. A panel of August (RT-1c; Ig kappa-1a) rat T helper clones specific for Id of syngeneic anti-Ig kappa-1b C3B9 monoclonal antibody (mAb) has been developed to study IdC3B9 presentation by Ig kappa-1b-bearing B cells from congenic August.1b (RT-1c; Ig kappa-1b) rats. Five of seven IdC3B9-specific T clones responded even at very low concentrations (100-200 pg/ml) of C3B9 mAb presented by Ig kappa-1b+ B cells. In contrast, the presentation of intact C3B9 mAb by nonspecific antigen-presenting cells (macrophages, Ig kappa-1a+ B cells, etc.) to IdC3B9-specific T cells was of low efficiency. The IdC3B9-specific T cell response to idiotopes of anti-Ig kappa-1b C3B9 mAb was found to be restricted by RT-1B molecule and required the processing of intact C3B9 molecule. IdC3B9 epitope recognized by C31 and C5 clones was mapped to the heavy chain of C3B9 mAb. Thus, B cells are able to present peptides related to the V region of anti-sIg Ab, i.e. Id peptide/MHC class II complexes, to Id-recognizing T cells. IdC3B9-presenting B cells are specifically activated both to proliferation and Ig production upon interaction with IdC3B9-specific T clones. Based on the results of our studies on B cell presentation of Ig epitopes to T cells a hypothetical model of Ig peptide-driven T-B cell interaction has been proposed.

Native IgG2ab is barely antigenic to major histocompatibility complexclass II‐restricted T cells owing to inefficient internalization by professionalantigen‐presenting cells

“…4a, lower left panel). Whereas B cells effectively present MHC class II‐associated peptides derived from their intrinsic immunoglobulin 12,18,30−32 or from immunoglobulin targeted to the B‐cell antigen receptor, 33 the above data are in agreement with studies showing that B cells inefficiently present soluble antigen via fluid‐phase endocytosis. 34 However, B cells do express CR, 35 which we considered might represent an entryway for IgG2a b immune complexes following C fixation.…”

Anti‐Tumour Activity of Idiotype‐Specific, MHC‐Restricted Th1 and Th2 Clones In Vitro and In Vivo

“…However. Id-specific T-cell lines and clones have now been established [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. some of which are MHC class 1 [31] or class II [24-29, 32, 35-39] restricted like conventional TcR 7.J!…”

The cellular mechanism by which complementary Id+ and anti‐Id antibodies communicate: T cells integrated into idiotypic regulation

“…Thus, in transfer studies, mice that received M315‐primed B cells, M315L chain‐primed T cells and M315 myeloma protein, developed an anti‐Id Ab response 15 . In addition, B cells whose BCR was ligated by an Ig allotype‐specific mAb, efficiently presented an Id‐peptide (derived from the allotype‐specific mAb) to T cells 16 . Finally, when recombinant Ig (rIg) with Id‐peptide genetically integrated to the C‐region were targeted to an IgD allotype on B cells, the Id‐peptide was efficiently presented on MHC class II molecules to Id‐specific CD4 + T cells in vivo 17 …”